Abstract
Drug-delivery vehicles have been used extensively to modulate the biodistribution of drugs for the purpose of maximizing their therapeutic effects while minimizing systemic toxicity. The release characteristics of the vehicle must be balanced with its encapsulation properties to achieve optimal delivery of the drug. An alternative approach is to design a delivery vehicle that preferentially releases its contents under specific endogenous (e.g., tissue pH) or exogenous (e.g., applied temperature) stimuli. In the present manuscript, we report on a novel delivery system with potential for triggered release using external beam radiation. Our group evaluated Zein protein as the basis for the delivery vehicle and used radiation as the exogenous stimulus. Proteins are known to react with free radicals, produced during irradiation in aqueous suspensions, leading to aggregation, fragmentation, amino acid modification, and proteolytic susceptibility. Additionally, we incorporated gold particles into the Zein protein matrix to create hybrid Zein–gold nanoparticles (ZAuNPs). Zein-only nanoparticles (ZNPs) and ZAuNPs were subsequently exposed to kVp radiation (single dose ranging from 2 to 80 Gy; fractionated doses of 2 Gy delivered 10 times) and characterized before and after irradiation. Our data indicated that the presence of gold particles within Zein particles was correlated with significantly higher levels of alterations to the protein, and was associated with higher rates of release of the encapsulated drug compound, Irinotecan. The aggregate results demonstrated a proof-of-principle that radiation can be used with gold nanoparticles to modulate the release rates of protein-based drug-delivery vehicles, such as ZNPs.
Highlights
Chemotherapy and radiation therapy are potent treatment modalities for cancer, but delivering curative doses to the tumor is often precluded by chemo- or radiotoxicity to normal tissue
Innovations in gantry design of radiation therapy (RT) machines to maximize delivery of high radiation doses safely to the tumor are close to their physical limits, but the variety of drug-delivery systems, some of which are already clinically used, could be modified to release their contents only when exposed to radiation
The ZAuNPs displayed higher baseline turbidity and absorbance at 280 nm when their Ultraviolet visible spectroscopy (UV–vis) characteristics were probed. This has been reported in the literature previously, and our results suggested alignment with this finding in that the incorporation of metallic nanoparticles, such as AuNPs, may influence the secondary and tertiary structure of the protein, thereby altering the absorption characteristics of the protein carrier [11,12]
Summary
Chemotherapy and radiation therapy are potent treatment modalities for cancer, but delivering curative doses to the tumor is often precluded by chemo- or radiotoxicity to normal tissue. Innovations in gantry design of radiation therapy (RT) machines to maximize delivery of high radiation doses safely to the tumor are close to their physical limits, but the variety of drug-delivery systems, some of which are already clinically used, could be modified to release their contents only when exposed to radiation. A protein-based matrix made from Zein was used to encapsulate gold nanoparticles (AuNPs) and a drug This Zein delivery system effectively encapsulated the drug with minimal release in the absence of the triggering mechanism. When the hybrid particles were irradiated, the protein matrix was modified and degraded by the radiation–gold particle interactions to release the drug on-demand Overall, this strategy would enable more precise drug delivery to the tumor, as only particles in the target local environment receiving radiation would release drugs. Specific and triggered delivery of the drugs by radiation has the potential to reduce systemic toxicities and, increase drug concentration levels within the tumor itself
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